Drug Database: Tenofovir-Based Microbicides

What are tenofovir-based microbicides? What are tenofovir-based microbicides?

What are tenofovir-based microbicides?

Tenofovir-based topical microbicides are investigational products that are being studied to prevent sexual transmission of HIV.^4-12 They have also been studied to prevent herpes simplex virus type 2 (HSV-2) infection.⁴

Tenofovir, the HIV drug used in tenofovir-based microbicides, belongs to a class of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).¹³ NRTIs block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and from spreading to other cells.

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do topical microbicides work? How do topical microbicides work?

How do topical microbicides work?

Topical microbicides come in many different forms, including gels, creams, films, and vaginal rings (also called intravaginal rings or IVRs). These products are designed to prevent HIV infection during sex, so they are used close to where HIV might enter the body during sexual activities – either the vagina or rectum.^13,14

Researchers have studied several different tenofovir-based microbicide products, including products for vaginal use (gel, film, tablet, intravaginal ring, and insert), as well as products for rectal use (gel, douche, and insert).^4–10,15,16 The tenofovir vaginal gel was the furthest along in development, but it failed to protect women from acquiring HIV in a Phase 3 trial.^4,17 Currently, the tenofovir rectal gel and intravaginal rings containing tenofovir are the most advanced products in Phase 2 developement.^5,8

Select clinical trials of tenofovir-based microbicides Select clinical trials of tenofovir-based microbicides

Select clinical trials of tenofovir-based microbicides

Tenofovir-based microbicides for rectal use

Rectal gel

Study Names: MTN-017; NCT01687218

Phase: 2
Status: This study has been completed.
Location: United States, Peru, Puerto Rico, South Africa, and Thailand
Purpose: The purpose of this study was to look at the safety and acceptability of tenofovir rectal gel (used either once daily or before and after sex [intermittently]) versus daily oral Truvada in men and transgender women without HIV.⁵
Selected Study Results: Results published in Clinical Infectious Diseases (2017) showed that tenofovir rectal gel was safe. Product adherence was comparable for both the intermittent gel and the daily oral Truvada regimens but was lower for the daily gel regimen. In terms of acceptability, participants liked using daily oral Truvada significantly more than either of the rectal gel regimens. When assessing ease of use and likelihood of future use for each regimen, there was no significant difference between the intermittent gel and the daily oral Truvada regimens.¹⁸
Additional Published Material:

• AIDS Behav article, 2017: Preference of oral tenofovir disoproxil fumarate/emtricitabine versus rectal tenofovir reduced-glycerin 1% gel regimens for HIV prevention among cisgender men and transgender women who engage in receptive anal intercourse with men
• PLoS One article, 2017: High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women

Additional studies looking at the rectal use of tenofovir gel have been completed, including:

• MTN-007 (NCT01232803): A Phase 1 study that tested the safety and acceptability of a tenofovir vaginal gel when applied rectally.¹⁹ Results are available from PLoS One (2013).
• CHARM-01 (NCT01575405) and CHARM-02 (NCT01575418): Phase 1 studies that evaluated the safety, acceptability, and pharmacokinetics of three different formulations of rectally-applied tenofovir gel: two vaginal formulations and a rectal formulation.^20,21 Results are available from PLoS One (2015) and AIDS Res Hum Retroviruses (2015).

Other rectal dosage forms

A tenofovir rectal douche or enema has been studied in four completed Phase 1 trials: DREAM-01 (NCT02750540), DREAM-02 (NCT04195776), DREAM-03 (NCT04016233) and ATN DREAM (NCT04686279).^9,10,22,23 Results to DREAM-01 are published in J Infect Dis (2024) and Sex Transm Infect (2024). DREAM-03 results are available from CROI 2022. ATN DREAM results are available from ClinicalTrials.gov.

Rectal inserts containing tenofovir alafenamide/elvitegravir are also in development. A Phase 1 study (MTN-039; NCT04047420) was completed, and results are available from J Infect Dis (2024) and CROI 2023.¹⁶ Another Phase 1 study (RITE Study; NCT06274398) is currently recruiting participants.¹²

Tenofovir-based vaginal microbicides

Vaginal gel

Study Names: FACTS 001; NCT01386294

Phase: 3
Status: This study has been completed.
Location: South Africa
Purpose: The purpose of this study was to look at the safety of tenofovir vaginal gel and to see how well the gel could protect women from getting HIV through sex.⁴
Selected Study Results: Results published in The Lancet Infectious Diseases (2018) showed that the use of tenofovir gel before and after sex appeared safe but did not prevent HIV infection in young women. The HIV incidence rate was the same in both the tenofovir gel and placebo groups — 4.0 cases per 100 women per year.¹⁷

Additional clinical trials evaluating tenofovir vaginal gel have also been completed. These include the Phase 2b CAPRISA 004 trial (NCT00441298) and the Phase 2b VOICE trial (MTN-003; NCT00705679).^24,25 Results to CAPRISA 004 are published in Science (2010) and results to the VOICE trial are available from the N Engl J Med (2015).

Intravaginal rings

Study Names: Protocol B17-144; NCT03762382

Phase: 2a 
Status: This study has been completed.
Location: Kenya
Purpose: The primary purpose of this study was to evaluate the safety of a multipurpose prevention technology IVR delivering both tenofovir and levonorgestrel and a tenofovir only IVR, each compared to a placebo IVR, in women from Kenya. Secondarily, researchers assessed the interactions between the drugs delivered by each IVR and the body (pharmacokinetics and pharmacodynamics), as well as IVR tolerability and acceptance.⁸
Selected Study Results: Results published in Frontiers in Reproductive Health (2023) showed that both the tenofovir and levonorgestrel IVR and the tenofovir only IVR used continuously for 90 days were safe. No genital lesions (sores) were seen by visual inspection. Data from the study indicated that the multipurpose tenofovir/levonorgestrel IVR has the potential to prevent HIV, HSV-2, and unintended pregnancy.²⁶
Additional Published Material:

• Sci Rep article, 2022: Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya

Additional Phase 1 studies of IVRs containing tenofovir have been conducted, including:

• MTN-038 (NCT03670355): A safety and pharmacokinetic study of a 90-day IVR containing tenofovir. This study has been completed, and results are published in J Int AIDS Soc (2024).²⁷
• CONRAD A13-128 (NCT02235662): A one-month safety, pharmacokinetic, and pharmacodynamic study of the tenofovir/levonorgestrel IVR and a tenofovir-only IVR. This study has been completed, and results are available from PLoS One (2018).²⁸
• CONRAD A15-138 (NCT03279120): A safety, pharmacokinetic, and pharmacodynamic study of a 90-day tenofovir/levonorgestrel IVR. This study has been completed. Results are published in PLoS One (2022).²⁹
• NCT03255915: A study evaluating the safety and pharmacokinetics of an IVR delivering both tenofovir disoproxil fumarate and emtricitabine (TDF-FTC pod-IVR). This study is ongoing, but not recruiting participants.³⁰

Other vaginal dosage forms

Other forms of tenofovir-based vaginal microbicides have been investigated in early-phase trials. These include a Phase 1 trial (NCT01694407) that evaluated vaginal tablets containing tenofovir and/or emtricitabine and a Phase 1 trial (FAME-04; NCT01989663) that assessed tenofovir vaginal gel and film formulations.^6,7 Results to FAME-04 are available from J Int AIDS Soc (2018).

Vaginal inserts containing tenofovir alafenamide and elvitegravir are also under development. A Phase 1 study (NCT03762772) was completed, and results are available from Front Cell Infect Microbiol (2023).¹⁵ Another Phase 1 study (MATRIX-001; NCT06087913) is currently recruiting participants.¹¹  

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might tenofovir-based microbicides cause? What side effects might tenofovir-based microbicides cause?

What side effects might tenofovir-based microbicides cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of tenofovir-based microbicides listed above.

MTN-017 (NCT01687218)

In this Phase 2 study that compared tenofovir rectal gel (used daily or intermittently) with oral Truvada, the gel was reported to be safe. Most side effects were mild or moderate in intensity. Rates of side effects (moderate intensity or higher) were similar for the tenofovir rectal gel groups and the oral Truvada group. Excluding rectal infections, the most common side effect of moderate intensity with the daily rectal gel and oral Truvada was diarrhea and headache, respectively.¹⁸

FACTS 001 (NCT01386294)

In this Phase 3 study, tenofovir vaginal gel was compared to a placebo vaginal gel. The number of participants who had side effects of moderate intensity was greater in the tenofovir group than in the placebo group. The most common product-related side effects of moderate or greater severity were very low levels of phosphate (hypophosphatemia), genital symptoms, and elevated liver enzyme levels. No product-related serious side effects occurred during the study. There were no notable differences between treatment groups in product-related side effects and severe or life-threatening side effects.¹⁷

Protocol B17-144 (NCT03762382)

In this Phase 2a trial evaluating the continuous use of a tenofovir/levonorgestrel IVR and a tenofovir-only IVR against a placebo IVR for up to 90 days, the most common side effects that occurred were bacterial vaginosis (a bacterial infection in the vagina), headache, and respiratory tract infections. The only product-related side effects that occurred were mild or moderate changes in menstrual bleeding patterns, which were reported in 6 participants using the tenofovir/levonorgestrel IVR and 1 participant using the tenofovir-only IVR.²⁶

Because tenofovir-based microbicides are still being studied, information on possible side effects of the products is not complete. As testing of tenofovir-based microbicides continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tenofovir-based microbicides? Where can I get more information about clinical trials studying tenofovir-based microbicides?

Where can I get more information about clinical trials studying tenofovir-based microbicides?

More information on research studies related to tenofovir-based microbicides is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References References

References

1. National Center for Biotechnology Information. PubChem compound summary for CID 464205, tenofovir. Accessed September 26, 2024
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Accessed September 26, 2024
3. Abdool Karim SS, Baxter C, Abdool Karim Q. Advancing HIV prevention using tenofovir-based pre-exposure prophylaxis. Antivir Ther. 2022;27(2):13596535211067589. doi:10.1177/13596535211067589. Accessed September 26, 2024
4. CONRAD. A Phase III, multi-centre, randomized controlled trial to assess the safety and effectiveness of the vaginal microbicide 1% tenofovir gel in the prevention of human immunodeficiency virus type 1 infection in women, and to examine effects of the microbicide on the incidence of herpes simplex virus type 2 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2011. NLM Identifier: NCT01386294. Accessed September 26, 2024
5. CONRAD. A Phase 2 randomized sequence open label expanded safety and acceptability study of oral emtricitabine/tenofovir disoproxil fumarate tablet and rectally-applied tenofovir reduced-glycerin 1% gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 27, 2012. NLM Identifier: NCT01687218. Accessed September 26, 2024
6. CONRAD. A Phase I clinical trial assessing the safety, pharmacokinetics, pharmacodynamics, and disintegration time of vaginal tablets containing tenofovir and/or emtricitabine. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 17, 2012. NLM Identifier: NCT01694407. Accessed September 26, 2024
7. CONRAD. A Phase I trial to assess the safety of tenofovir gel and film formulations: FAME 04. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 5, 2013. NLM Identifier: NCT01989663. Accessed September 26, 2024
8. CONRAD. Phase IIa, 90-day safety, adherence, and acceptability study of intravaginal rings releasing tenofovir with and without levonorgestrel among women in Western Kenya. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762382. Accessed September 26, 2024
9. Johns Hopkins University. A Phase 1 open label study evaluating the distribution of a tenofovir douche in combination with tap water douching and simulated receptive anal intercourse (DREAM-02). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 10, 2019. NLM Identifier: NCT04195776. Accessed September 26, 2024
10. Johns Hopkins University. A Phase I, open-label multiple dose safety, pharmacokinetic, pharmacodynamic, and acceptability study of tenofovir rectal douche. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 9, 2019. NLM Identifier: NCT04016233. Accessed September 26, 2024
11. Eastern Virginia Medical School. A Phase I randomized, placebo-controlled, double-blind study to assess safety, pharmacokinetics, and modeled pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 7, 2023. NLM Identifier: NCT06087913. Accessed September 26, 2024
12. Eastern Virginia Medical School. A double-blind, placebo-controlled, randomized Phase 1 study to evaluate the safety and pharmacokinetics of rectally administered tenofovir alafenamide/elvitegravir inserts. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 31, 2024. NLM Identifier: NCT06274398. Accessed September 26, 2024
13. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385. Accessed September 26, 2024
14. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV.  Accessed September 26, 2024
15. CONRAD. A Phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762772. Accessed September 26, 2024
16. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1 open label safety and pharmacokinetic study of rectal administration of a tenofovir alafenamide/elvitegravir insert at two dose levels. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 5, 2019. NLM Identifier: NCT04047420. Accessed September 26, 2024
17. Delany-Moretlwe S, Lombard C, Baron D, et al. Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018;18(11):1241-1250. doi:10.1016/S1473-3099(18)30428-6. Accessed September 26, 2024
18. Cranston RD, Lama JR, Richardson BA, et al. MTN-017: a rectal Phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel. Clin Infect Dis. 2017;64(5):614-620. doi:10.1093/cid/ciw832. Accessed September 26, 2024
19. CONRAD. A Phase 1 randomized, double-blinded, placebo-controlled rectal safety and acceptability study of tenofovir 1% gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 1, 2010. NLM Identifier: NCT01232803. Accessed September 26, 2024
20. Ian McGowan. A randomized, double blind Phase 1 safety, acceptability, and pharmacokinetic study comparing three formulations of tenofovir 1% gel administered rectally to HIV-1 seronegative adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 29, 2012. NLM Identifier: NCT01575405. Accessed September 26, 2024
21. Ian McGowan. An exploratory, double-blinded, randomized, pharmacokinetic and safety study of three rectally-applied tenofovir 1% microbicide gel formulations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01575418. Accessed September 26, 2024
22. Johns Hopkins University. DREAM-01: optimization of a tenofovir enema for HIV prevention. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 11, 2016. NLM Identifier: NCT02750540. Accessed September 26, 2024
23. University of Pennsylvania. Safety, PK/PD, acceptability, and desirability of a novel HIV prevention douche among adolescent men (DREAM). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 22, 2020. NLM Identifier: NCT04686279. Accessed September 26, 2024
24. Centre for the AIDS Programme of Research in South Africa. Phase IIb trial to assess the safety and effectiveness of the vaginal microbicide 1% tenofovir gel for the prevention of HIV infection in women in South Africa. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2007. NLM Identifier: NCT00441298. Accessed September 26, 2024
25. National Institute of Allergy and Infectious Diseases (NIAID). Phase 2B safety and effectiveness study of tenofovir 1% gel, tenofovir disoproxil fumarate tablet and emtricitabine/tenofovir disoproxil fumarate tablet for the prevention of HIV infection in women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2008. NLM Identifier: NCT00705679. Accessed September 26, 2024
26. Mugo NR, Mudhune V, Heffron R, et al. Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya. Front Reprod Health. 2023;5:1118030. doi:10.3389/frph.2023.1118030. Accessed September 26, 2024
27. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1, randomized pharmacokinetic and safety study of a 90 Day intravaginal ring containing tenofovir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 12, 2018. NLM Identifier: NCT03670355. Accessed September 26, 2024
28. CONRAD. Phase I one-month safety, pharmacokinetic, pharmacodynamic, and acceptability study of intravaginal rings releasing tenofovir and levonorgestrel or tenofovir alone. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 14, 2014. NLM Identifier: NCT02235662. Accessed September 26, 2024
29. CONRAD. Phase I, 90-Day safety, pharmacokinetic, and pharmacodynamic study of intravaginal rings releasing tenofovir and levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 23, 2017. NLM Identifier: NCT03279120. Accessed September 26, 2024
30. Oak Crest Institute of Science. Randomized order, controlled, double blind, crossover early Phase 1 pilot study to assess safety and pharmacokinetics of a tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) releasing IVR over 28 days compared to placebo. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2017. NLM Identifier: NCT03255915. Accessed September 26, 2024